There has been a great deal of attention directed towards the elaboration of organic compounds from readily available building blocks. One reason for such attention relates to the synthesis of pharmaceutical molecules, synthetic polymers, pesticides, food supplements, and a host of other, useful materials. Moreover, the preparation of electronics chemicals can benefit greatly from improved synthetic schemes. Of particular importance is the coupling of compounds between their respective carbon atoms, which is an important tool for synthesizing and building organic compounds. The coupling of compounds is usually complicated due to sensitivity of different functional groups on the compounds to the reaction conditions or catalysts. While some methods for coupling compounds are available, they do not always offer the efficiencies or economies required for large scale production and are not appropriate for all syntheses. Accordingly, there is continuing interest in improving methods of synthesis involving carbon-carbon coupling, called cross-coupling when between different organic molecules.
The art of cross-coupling reactions catalyzed by palladium catalysts is a powerful method to combine organic molecules by joining their carbon atoms. In the Suzuki cross-coupling reaction, carbon atoms of a boronic acid and an aryl halide are coupled via palladium catalysis under basic conditions. Recently, palladium catalysts, such as Pd(PPh3)4, have been used with the Suzuki reaction to cross-couple an aryl or a vinyl boronic acid to an aryl or vinyl halide or triflate. Certain other palladium catalysts, like PdCl2(dppf) and Pd(OAc)2, are also available. Primary alkyl groups can also be transferred by the Suzuki reaction using 9-BBN reagents and PDCl2(dppf) as a catalyst.
A category of palladium catalysts useful in cross-coupling reactions are palladium-phosphine complexes. In one example, Sunagawa et al., U.S. Pat. No. 5,216,186, describe the synthesis of crystalline palladium tetrakis (triphenylphosphine) or Pd(PPh3)4. Sunagawa et al. also describe palladium tetrakis (triphenylphosphine) to be useful in the field of organic synthesis, explaining its use as a catalyst for deprotecting reactions of allyl esters or allyl ethers or allylation reactions of carbon or nitrogen atoms. Beller et al. in U.S. Pat. No. 5,831,107 describe a number of palladacycles and their importance as catalysts for processes such as the synthesis of substituted styrenes, preparation of stilbenes and cinnamic acids from aryl halides.
Despite the usefulness of palladium-phosphine complexes and their use in cross-coupling reactions, the use of phosphine ligands often can result in side reactions such as phosphonium salt formation and ary-aryl exchange between substrate and phosphine. In addition, it is known that highly sensitive compounds often do not tolerate the basic conditions required by the Suzuki reaction. Also, this reaction requires extensive refluxing of the reaction mixtures. Furthermore, a popular phosphine catalyst, tri-tert-butylphosphine is known to be very expensive and may not be practicable for large scale production of materials.
Accordingly, there still remains a need for an economical, selective and efficient means for cross-coupling of compounds, particularly aryl compounds, via their respective carbon atoms. Further, there is a need for an economical, selective and efficient cross-coupling reaction that provides mild conditions for the synthesis of aryl derivates such as arylpyridines and aryl anilines, particularly sterically hindered ortho-substituted anilines.